Neurosurgery 1992-98 eyelid of 2 months' duration that was followed within

January 1994, Volume 34, Number 1 1 month by frank ptosis, and later by diplopia. There
163 Intracranial Suprasellar Angiolipoma: was no other complaints.
Ultrastructural and Immunohistochemical Features At the time of the hospital admission, her mental
Case Report status and higher cognitive functions were normal.
She had normal visual acuity while wearing
AUTHOR(S): corrective lenses, and her visual fields were normal to
Lach, Boleslaw, M.D., Ph.D., F.R.C.P.(C.); confrontation. There was an incomplete left third
Lesiuk, Howard, M.D, F.R.C.S.(C.) nerve palsy with partial involvement of the left pupil.
The remaining cranial nerves were intact. The
Department of Laboratory Medicine (BL) and findings of the neurological and general examinations
Division of Neurosurgery (HL), Ottawa Civic were otherwise unremarkable. Laboratory evaluations
Hospital and University of Ottawa, Ottawa, Canada of endocrine function revealed normal pituitary
function with maintenance of adequate target gland
Neurosurgery 34; 163-167, 1994 hormone levels.
Computed tomographic and magnetic resonance
ABSTRACT: THE AUTHORS PRESENT imaging of the brain with high-resolution and direct
ultrastructural and immunohistochemical coronal views of the sellar region revealed a sellar
characteristics of an intracranial suprasellar tumor and left parasellar tumor measuring approximately 5
displaying features of cavernous angioma with islets × 3 × 3 cm, (Fig. 1). There was expansion of the sella
of adipose tissue. Electron microscopy revealed thin- turcica without significant bone erosion. Cerebral
walled vessels separated by a loose collagenous angiography demonstrated an avascular mass
stroma containing nests of mature adipocytes as well extending to the left cavernous sinus. On the basis of
as fibroblasts, myofibroblasts, mast cells, and a few both the clinical and radiographic findings, a
macrophages. Intracytoplasmic lipid droplets were nonfunctioning pituitary adenoma was suspected.
also identified in scattered pericytes and smooth The patient underwent a left frontotemporal
muscle cells of vascular walls and in the transitional craniotomy. At surgery, a well-circumscribed,

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cells resembling smooth muscle cells and adipocytes. seemingly encapsulated, red-purple sellar and left
Many adipose tissue cells were positive for S-100 parasellar lesion was found. The tumor appeared to be
protein with polyclonal antibodies. Other lipidized composed of a meshwork of large, thin-walled
tumor cells were immunoreactive for some or all of vascular channels that bled profusely during surgical
the following: smooth muscle-specific actin, factor manipulation. Only scant spicules of solid tissue were
XIIIa, vimentin, and, occasionally, for desmin. encountered within the vascular "lakes." Some
Ultrastructure and immunohistochemistry indicate reduction in the volume of the mass was achieved by
that in addition to typical adipocytes, lipidized cells partial resection and by the aspiration of blood.
of another nature contribute to the characteristic Hemostasis was obtained with absorbable gelatin
appearance of the adipose tissue component of sterile sponge (Gelfoam, The Upjohn Co.,
angiolipoma. Kalamazoo, MI) packing. The patient had an
unremarkable postoperative course with gradual
KEY WORDS: Angiolipoma; Electron microscopy; resolution of the left third nerve palsy.
Immunohistochemistry; Intrasellar tumors
METHODS
Angiolipomas are benign mesenchymal neoplasms Paraffin-embedded and frozen samples of the
composed of an intimate mixture of blood vessels and tumor were examined by staining sections with
mature adipose tissue (2,9,13,17,20,23,26-28). These tumors hemotoxylin and eosin and oil red O as well as by the
are most often benign and usually occur in the peroxidase-antiperoxidase (25) and avidin-biotin-
subcutaneous tissue of the upper extremities and peroxidase (10) methods for immunohistochemical
trunk of young adults (2,9,13). Within the craniospinal localization of the antigens listed in Table 1, which
axis, angiolipomas are extremely rare, and almost all summarized the dilutions, distributors, and
have been found in the spinal extradural space (17,20, immunoreactivities of the antisera. Each set of slides
23,27)
. Only two patients with intracranial used for immunohistochemical study was
angiolipomas have been reported; on both occasions, accompanied by control sections known to contain
the tumors were in close association with the middle cells positive for the examined antigen. For negative
cranial fossa and sphenoid sinus (26,28). Here we controls, buffered saline was substituted for the first
describe the immunohistochemical and electron layer of specific antibodies.
microscopic features of a suprasellar angiolipoma For transmission electron microscopy, small
extending to the sphenoid sinus and the perisellar samples of the tumor were quickly immersed in 1.6%
areas of the middle cranial fossa. glutaraldehyde and processed in a routine fashion to
Epon Araldite (Marivac Ltd., Halifax, Canada)
CLINICAL HISTORY embedding and staining with uranyl acetate and lead
The patient, a 65-year-old, right-handed woman citrate (14). Grids were examined using a Hitashi H-
who was a native of the Bahamas, was referred to an 7100 electron microscope.
endocrinologist for evaluation of insidiously
progressive easy fatigability and heaviness of the left RESULTS
 Light microscopy revealed a very vascular tumor intradigitating processes so characteristic of
composed of dilated capillaries and cavernous vessels neoplastic arachnoidal cells in meningiomas.
with occasional parietal or occluding thrombi
(Fig. 2a). The walls of some vessels were almost DISCUSSION
acellular and fibrotic, with a flattened single layer of The clinical and morphological features in this case
endothelium, while others showed a few layers of very closely resemble those of two previously
smooth muscle cells. A scanty interstitium consisted reported examples of intracranial suprasellar
of nests of mature adipose tissue and minimal angiolipomas (26,28). At the level of light microscopy,
amounts of collagenous stroma, with a few the neoplasm presented here is essentially an
mononuclear lymphoid cells and mast cells. The angioma with islands of adipose tissue. The
tumor contained small fragments of dura and focally submicroscopic features and absence of
extended to the underlying bone of the adjacent immunoreactivity with monoclonal antibodies for the
sphenoid wing. There was no evidence of arachnoid epithelial membrane antigen exclude a remote
differentiation or psammoma body formation. possibility of a vascular lipoblastic meningioma (12).
The ultrastructural and immunohistochemical
Immunohistochemical study properties of the tumor indicate two predominant
Immunohistochemical study revealed strong patterns of cellular differentiation: 1) to the major
reactions for vimentin and actin in smooth muscle cellular components of vascular walls (endothelium,
cells and occasional lipidized cells as well as in some smooth muscle cells, and pericytes), and 2) to mature
pericytes and endothelial cells (Fig. 2b). Smooth adipose tissue. The ultrastructural features of the
muscle cells were also positive for desmin. Flattened majority of lipidized cells as well as their S-100
endothelial cells lining the vascular lumina were immunoreactivity are similar to those of normal
immunoreactive for factor VIII-related antigen and adipose tissue and low-grade lipomatous tumors,
with Ulex europeus lectin. Factor XIIIa was indicating the true differentiation of adipose tissue in
demonstrated in many cells representing either this lesion (5,6). The expression of factor VIII-related
macrophages or pericyte-like cells in the antigen and Ulex Europeus lectin receptors in the
subendothelial stroma. Occasional factor XIIIa- endothelium, as well as actin, vimentin, and desmin

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positive cells showed vacuolated cytoplasm, in the smooth muscle cells, are all consistent with
suggesting the presence of intracytoplasmic lipids. differentiation to cells forming vascular walls.
Nuclei and cytoplasm of adipose cells were Some lipid-containing cells in this tumor were very
immunoreactive for S-100 protein with polyclonal similar to the subpopulation of so-called stromal cells
antibodies. Occasional endothelial nuclei were of hemangioblastomas, considered to be a modified
positive with monoclonal antibodies against form of endothelium (7) or pericytes and smooth
proliferating cell nuclear antigen. muscle cells (11). Moreover, the immunoreaction of
some vacuolated cells with antibodies against factor
Electron microscopy XIIIa, in conjunction with electron microscopy,
Electron microscopy revealed numerous capillaries indicate lipidization of fibrohistiocytic cells (24), a
lined by a single layer of fenestrated endothelial cells phenomenon also observed in the cerebellar
(Fig. 3). Endothelial cell membranes formed a hemangioblastomas (15). Although some vascular
profusion of intraluminal surface projections as well tumors may express low molecular weight
as lateral intradigitations with adjacent endothelial cytokeratin, (3), AE1 and AE3 monoclonal antibodies
and smooth muscle cells. Weibel-Palade bodies were were nonreactive in this case. A small number of cells
commonly found. The scanty subendothelial tissue positive for proliferating cell nuclear antigen is
showed the presence of pericytes, smooth muscle consistent with a slowly progressive clinical course
cells, fibroblasts, myofibroblasts, a few macrophages, and the benign nature of this lesion. Interestingly,
and mast cells, as well as lipidized cells with variable only the capillary endothelial cells represented the
amounts of intracytoplasmic lipids (Figs. 3, 4, 5, 6). exclusive pool of dividing cells. This indicates that
The majority of cells containing lipids displayed proliferation of endothelium, rather than precursor
ultrastructural features of typical adipocytes with non- cells in the stroma, led to the growth of new
membrane-bound lipid vacuoles of various sizes capillaries and expansion of this tumor.
occupying most of the cytoplasm (Fig. 4). Varying The presence of well-differentiated smooth muscle
numbers of cytoplasmic fat droplets were also present cell points to the histological similarities of this
in the smooth muscle cells and pericytes (Figs. 3 and lesion to another tumor of vascular origin, the
5). Moreover, they were seen in the cells with angiomyolipoma (1,8,16,18,19). Like angiolipomas,
transitional morphological features reminiscent of angiomyolipomas are benign, noninfiltrating tumors
those smooth muscle cells or pericytes, and those of composed of a variable mixture of smooth muscle
adipocytes (Fig. 6). These "transitional" cell types cells, blood vessels, and adipose tissue. However,
were partially surrounded by discontinuous external they usually occur in kidneys in patients with
lamina, usually with adjacent subsarcolemmal tuberous sclerosis (1,4,19,23), and rarely in an extrarenal
attachment plaques. The cytoplasm contained many location (18,23). As in our case, lipidization of smooth
micropinocytic vesicles, scanty intermediate muscle cells and the occurrence of transitional cells
filaments, and small amounts of endoplasmic with features of smooth muscle cells or pericytes and
reticulum. Lipidized cells showed no evidence of adipocytes have been observed in these tumors (1,8,16,
18,19)
desmosomes or hemidesmosomes, and no . These ultrastructural features and the close
histogenetic relation between angiolipomas and hemangioblastoma. I. Weibel-Palade bodies
angiomyolipomas makes distinguishing them as and stromal cell histogenesis. J Neuropathol
entities extremely difficult in some cases. An absence Exp Neurol 43:592-608, 1984.
of smooth muscle differentiation beyond the limits of 8. Holm-Nielson P, Serenson FB: Renal
the vascular walls argues against the inclusion of this angiomyolipoma: An ultrastructural
tumor in the group of angiomyolipomas. Although investigation of three cases with histologic
extradural spinal angiomyolipomas have been considerations. Acta Pathol Microbiol
described (18), no cases have been reported in the Immunol Scand [Suppl] 4:37-47, 1988.
intracranial location. 9. Howard WR, Helwig EB: Angiolipoma. Arch
Angiomyolipomas and angiolipomas represent Dermatol 82; 824-931, 1960.
mesenchymal hamartomas composed of abnormally 10. Hsu SM, Raine L, Fanger H: Use of avidin-
differentiated vessels and adipose tissue. This biotin-peroxidase complex (ABC) in
intricate mixture of adipose tissue and cells forming immunoperoxidase techniques. A comparison
vascular walls suggests that all these cell types may between ABC and unlabelled antibody (PAP)
arise from a common precursor (1,16). A shared origin procedures. J Histochem Cytochem 29:577-
of closely related vascular wall components such as 580, 1981.
endothelium, pericytes, and smooth muscle cells is 11. Kamitani H, Masuzawa H, Sato J, Kanazawa I:
widely accepted (21,22). Recent immunohistochemical Capillary hemangioblastoma. Histogenesis of
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relation of vascular and adipose tissues may explain 12. Kepes JJ: Meningiomas: Biology, Pathology
why some tumors with an angiomatous pattern of and Differential Diagnosis. New York,
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ACKNOWLEDGMENTS 34:720-727, 1974.

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The authors are very grateful to Mr. Allistair 14. McDowell CM: Fixation and processing, in
Gregor and Mrs. Barbara Williams-Kosabek from the Trump BJ, Jones RT (eds): Diagnostic
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Accepted, June 25, 1993. 16. Okada K, Okayama S, Nakayama I, Tada I,
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C.P.(C.), Department of Laboratory Medicine, 1053 hepatic angiomyolipoma. Acta Pathol Jpn
Carling Avenue, Ottawa K1Y 4E9, Canada. 39:743-749, 1989.
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COMMENTS

Redistribution of this article permitted only in accordance with the publisher’s copyright provisions.
The authors describe a unique intracranial example
of a lesion largely confined in its occurrence to the
spinal epidural space. Of particular interest is their
finding that it consisted not purely of mature
adipocytes and blood vessels, but also of pericytes
and vascular smooth muscles cells undergoing
lipidization. Whether, as the authors suggest,
angiolipomas represent mesenchymal hamartomas
arising from a common precursor remains to be
established, but their comparison of the lesion to
renal angiomyolipoma is entirely appropriate.

Bernd W. Scheithauer
Rochester, Minnesota
The authors have documented in exquisite detail
the pathology of a rare suprasellar angiolipoma. It is
important to document that this type of vascular
lesion can mimic a more common pituitary adenoma.
The detailed pathological analysis serves as an
excellent baseline for future angiolipomas that may
be discovered in intracranial locations. It also
provides an interesting comparison with other,
similar, pathological entities such as
hemangioblastomas and angiomyolipomas.

William F. Chandler
Ann Arbor, Michigan
Figure 1. Horizontal and coronal computed
tomographic scans showing a well-demarcated sellar
and suprasellar tumor extending to the adjacent
sphenoid sinus.

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Figure 2. a, Low-power photomicrograph showing
nests of adipose tissue (arrow) and cavernous vessels
filled with blood. b, Layers of smooth muscle cells
positive with anti-actin antibodies (arrow) in the
subendothelial area of many vessels.
Figure 3. Photomicrograph of a cavernous vessel
lined with endothelium. The subendothelial smooth
muscle cell corresponds to the area of
immunoreactivity for actin in Figure 1b. The stroma
contains many lipidized cells with subplasmolemmal
densities and short segments of basal lamina (arrows)
(magnification, ×10,050).

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Figure 4. A typical adipocyte with one large fat
droplet at the top and numerous small fat vacuoles
throughout the cytoplasm. The external lamina
around the cell is continuous, with a "corona" of
collagen fibers. (magnification, ×10,000).
Figure 5. Portion of subendothelial lipidized cells
with the characteristics of a typical smooth muscle
cell. Small arrows point to scattered pinocytic
vesicles. Curved arrows indicate subplasmolemmal
densities with microfilaments and surrounding
external lamina (magnification, ×26,200).

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Figure 6. Subendothelial lipidized cells showing
features of smooth muscle cell or a pericyte. Small
arrows point to pinocytic vesicles. Curved arrow
indicates segments of external lamina and
subsarcolemmal densities. The capillary lumen is at
the right (magnification, ×21,850).
 Paraffin-embedded Sections
Table 1. Immunoreactivities of Antibodies:

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